Induction of ethinylestradiol and levonorgestrel metabolism by oxcarbazepine in healthy women

Purpose: To evaluate the effect of oxcarbazepine (OCBZ) on the pharmacokine tic profile of steroid oral contraceptives. Methods: Twenty-two healthy women aged 18-44 years were recruited, and 16 o f them completed the study. By using a randomized double-blind crossover de sign, each woman was studied in two different menstrual cycles, during whic h placebo or OCBZ (maintenance dosage, 1,200 mg/day) was given in randomize d sequence for 26 consecutive days with a washout of at least one cycle in between. A steroid oral contraceptive containing 50 mu g ethinylestradiol ( EE) and 250 mu g levonorgestrel (LN) was taken for the first 21 days of eac h cycle. Plasma concentrations of EE and LN were measured by gas chromatogr aphy-mass spectrometry in samples collected at regular intervals on days 21 -23 of each cycle. Results: Compared with placebo, areas under the plasma concentration curves (AUC(0-24h), geometric means) decreased by 47% for both EE (from 1,677 to 886 pg.h/ml; p < 0.01) and LN (from 137 to 73 ng.h/ml; p < 0.01), during OC BZ treatment. Peak plasma EE concentrations decreased from 180 pg/ml during the placebo cycle to 117 pg/ml during the OCBZ cycle (p < 0.01), whereas p eak plasma LN concentrations decreased from 10.2 to 7.7 ng/ml (p < 0.01). T he half-lives of EE and LN also decreased from 13.6 to 7.9 h (p < 0.01) and from 28.8 to 15.8 h, respectively (p < 0.01). Conclusions: OCBZ reduces plasma concentrations of the estrogen and progest agen components of steroid oral contraceptives, presumably by stimulating t heir CYP3A-mediated metabolism in the liver or gastrointestinal tract or bo th. Because this may lead to a decreased efficacy of the contraceptive pill , women treated with OCBZ should receive preferentially a high-dosage contr aceptive and should be monitored for signs of reduced hormonal cover.